This invention relates to bis-esters of methanediol wherein one of the hydroxy groups of the methanediol is esterified with hetacillin (or the p-hydroxy analog thereof), and the other hydroxy group of the methanediol is esterified with penicillanic acid 1,1-dioxide. These compounds have particular value in mammals as oral antibacterial agents against penicillinase producing bacteria. They are efficiently absorbed from the gastrointestinal tract. After absorption they are transformed, providing unusually long-lasting serum levels of ampicillin/amoxicillin and penicillanic acid 1,1-dioxide. By its penicillinase inhibitory activity, the latter enhances the activity of the former against penicillinase producing bacteria.
The present compounds are acetonide derivatives of compounds earlier described in British patent application Ser. No. 2,044,255 and U.S. Pat. No. 4,244,951. Unexpectedly the present compounds show a greatly increased serum half-life of ampicillin/amoxicillin and penicillanic acid 1,1-dioxide in comparison to the parent compounds disclosed in these references.
Hetacillin (and the p-hydroxy analog thereof) have been described in the literature [Handcastle et al., J. Org. Chem. 31, pp. 897-899 (1966); Long et al., J. Chem. Soc. (C); pp. 1920-1922 (1971)]. Esters of hetacillin (and of the p-hydroxy analog thereof) have also been reported as especially usable for oral administration (von Daehne, U.S. Pat. No. 3,954,735, see also Sleezer et al., U.S. Pat. No. 4,185,015), but these compounds are not known to be beta-lactamase inhibitors.